Studies on integrinα3β1-mediated signaling

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The α3β1 integrin-mediated signaling events triggered by cell adhesion to laminin-10/11(LN-10/11) are quite different from those triggered by adhesion to fibronectin (FN). LN-10/11 preferentially activates Rac, but not Rho, through an α3β1 integrin-dependent pathway involving a p130Cas-CrkII-DOCK18O complex, thereby strongly promoting cell migration through enhanced formation of lamellipodia. On the other hand, the intracellular signaling pathways regulating cell survival focusing on two distinct signaling pathways involving PI 3-kinase/Akt and MEKi/ERK have been investigated. LN-10/11 is more potent than FN in suppressing apoptosis induced by serum deprivations The anti-apoptotic effects of LN-10I11 could be inhibited by the PI 3-kinase inhibitor wortmannin, whereas the anti-apoptotic effects of FN were inhibited by the MEKi inhibitor PD98059. Our results provide clear evidence that different signaling pathways leading to cell survival are activated, on different ECM ligands. Furthermore, remodeling of N-glycans of the integrin could also modulate its ligand binding and integrin-mediated signaling. Since laminins are the major components of the basement membrane of epithelium, our work supports the notion that a function of the basement membrane is to provide distinctive cell survival signals for establishment and maintenance of epithelial tissue.